Initiating GLP-1 Therapy in Combination with FreeStyle Libre Provides Greater Benefit Compared to GLP-1 Therapy Alone.

BACKGROUND AND AIM: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) therapy provides glycemic benefits to individuals with type 2 diabetes (T2D). However, the effects of GLP-1 RA therapy in combination with FreeStyle Libre systems (FSL) are unknown. This study aimed to compare changes in HbA1c between people acquiring GLP-1 with FSL (GLP-1+FSL) vs. GLP-1 without FSL (GLP-1). METHODS: This real-world study utilized Optum's de-identified Market Clarity Data, a linked electronic health records (EHR)-claims database and included adults with T2D and HbA1c ≥8% who acquired their first GLP-1 RA medication between 2018-2022. GLP-1+FSL subjects acquired their first FSL within ±30 days of their first GLP-1 acquisition. Cohorts were matched 1:5 on baseline insulin therapy, age, sex, baseline HbA1c and GLP-1 type. Paired changes in HbA1c were compared between unmatched and matched groups at six months. RESULTS: The study included 24,724 adults in the unmatched cohort (GLP-1+FSL, n=478; GLP-1, n=24,246). The matched cohort included 478 GLP-1+FSL users and 2,390 GLP-1 users: mean age 53.5±11.8 and 53.5 ±11.3 years, HbA1c 10.25±1.68% and 10.22±1.69%, respectively. HbA1c reduction was greater in the GLP-1+FSL group compared to the GLP-1 group in the unmatched cohort (-2.43% vs. -1.73%, difference 0.70%, p<0.001, respectively) and in the matched cohort (-2.43% vs. -2.06%, difference 0.37%, p<0.001). GLP-1+FSL vs. GLP-1 treatment was associated with greater HbA1c reduction in the intensive insulin (-2.32% vs. -1.50%), non-intensive insulin (-2.50% vs. 1.74%), and noninsulin group (-2.46% vs. -1.78%), as well as in patients using semaglutide (2.73% vs. 1.92%) and dulaglutide (2.45% vs. 1.71%) GLP-1 RA, all p<0.001. CONCLUSIONS: Adults with sub-optimally controlled T2D, initiating GLP-1 RA with FreeStyle Libre, had greater improvement in HbA1c compared to those treated with GLP-1 RA only. These results suggest an additional glycemic benefit of FSL when used with a GLP-1 RA in T2D treatment.

Insertable cardiac monitoring results in higher rates of atrial fibrillation diagnosis and oral anticoagulation prescription after ischaemic stroke.

AIMS: After an ischaemic stroke, atrial fibrillation (AF) detection allows for improved secondary prevention strategies. This study aimed to compare AF detection and oral anticoagulant (OAC) initiation in patients with an insertable cardiac monitor (ICM) vs. external cardiac monitor (ECM) after ischaemic stroke. METHODS AND RESULTS: Medicare Fee-for-Service (FFS) insurance claims and Abbott Labs device registration data were used to identify patients hospitalized with an ischaemic stroke in 2017-2019 who received an ICM or ECM within 3 months. Patients with continuous Medicare FFS insurance and prescription drug enrolment in the prior year were included. Patients with prior AF, atrial flutter, cardiac devices, or OAC were excluded. Insertable cardiac monitor and ECM patients were propensity score matched 1:4 on demographics, comorbidities, and stroke hospitalization characteristics. The outcomes of interest were AF detection and OAC initiation evaluated with Kaplan-Meier and Cox proportional hazard regression analyses. A total of 5702 Medicare beneficiaries (ICM, n = 444; ECM, n = 5258) met inclusion criteria. The matched cohort consisted of 2210 Medicare beneficiaries (ICM, n = 442; ECM, n = 1768) with 53% female, mean age 75 years, and mean CHA2DS2-VASc score 4.6 (1.6). Insertable cardiac monitor use was associated with a higher probability of AF detection [(hazard ratio (HR) 2.88, 95% confidence interval (CI) (2.31, 3.59)] and OAC initiation [HR 2.91, CI (2.28, 3.72)] compared to patients monitored only with ECM. CONCLUSION: Patients with an ischaemic stroke monitored with an ICM were almost three times more likely to be diagnosed with AF and to be prescribed OAC compared to patients who received ECM only.

Smartphone-based cardiac implantable electronic device remote monitoring: improved compliance and connectivity.

Aims: Remote monitoring (RM) is the standard of care for follow up of patients with cardiac implantable electronic devices. The aim of this study was to compare smartphone-based RM (SM-RM) using patient applications (myMerlinPulse™ app) with traditional bedside monitor RM (BM-RM). Methods and results: The retrospective study included de-identified US patients who received either SM-RM or BM-RM capable of implantable cardioverter defibrillators or cardiac resynchronization therapy defibrillators (Abbott, USA). Patients in SM-RM and BM-RM groups were propensity-score matched on age and gender, device type, implant year, and month. Compliance with RM was quantified as the proportion of patients enrolling in the RM system (Merlin.net™) and transmitting data at least once. Connectivity was measured by the median number of days between consecutive transmissions per patient. Of the initial 9714 patients with SM-RM and 26 679 patients with BM-RM, 9397 patients from each group were matched. Remote monitoring compliance was higher in SM-RM; significantly more patients with SM-RM were enrolled in RM compared with BM-RM (94.4 vs. 85.0%, P < 0.001), similar number of patients in the SM-RM group paired their device (95.1 vs. 95.0%, P = 0.77), but more SM-RM patients transmitted at least once (98.1 vs. 94.3%, P < 0.001). Connectivity was significantly higher in the SM-RM, with patients transmitting data every 1.2 (1.1, 1.7) vs. every 1.7 (1.5, 2.0) days with BM-RM (P < 0.001) and remained better over time. Significantly more SM-RM patients utilized patient-initiated transmissions compared with BM-RM (55.6 vs. 28.1%, P < 0.001). Conclusion: In this large real-world study, patients with SM-RM demonstrated improved compliance and connectivity compared with BM-RM.

Evaluation of cardiovascular implantable electronic device leads post implant: ElectroPhysiology Predictable And SuStainable Implementation Of National Registries (EP PASSION).

Post-market evaluation is important to ensure the ongoing safety and effectiveness of cardiovascular implantable electronic device (CIED) leads. The Twenty-First Century Cures Act and subsequent Food and Drug Administrative (FDA) Guidance provide an opportunity to leverage real-world data sources for this purpose. The past 4 years have seen the development of EP PASSION: a multi-stakeholder, collaborative effort between the FDA, CIED manufacturers, Heart Rhythm Society, and academics. Using real-world data, EP PASSION enables longitudinal evaluation of the long-term safety of CIED leads, addressing limitations of current approaches to generate evidence that informs regulatory, clinical, and manufacturer decision-making. This state of the art article describes the impetus for and launch of EP PASSION, the lessons learned, its current state, the current analytic approach, and the strengths and limitations of leveraging extant data sources for post-market lead evaluation. We also compare EP PASSION to traditional post-approval studies and describe possible future directions.

Arrhythmic Burden and the Risk of Cardiovascular Outcomes in Patients With Paroxysmal Atrial Fibrillation and Cardiac Implanted Electronic Devices.

BACKGROUND: Whether the amount of atrial fibrillation (AF) patients experience conveys important prognostic information beyond that provided by the diagnosis of AF is uncertain. The study objective was to assess the dose-response relationship between device-detected AF burden and subsequent cardiovascular outcomes. METHODS: Among patients with paroxysmal AF who underwent cardiac implantable electronic device implantation (2010-2016), Merlin.net remote-monitoring data were linked to Medicare claims to assess the magnitude and strength of the associations between device-based AF burden (defined as a daily percentage of time spent in AF or maximal AF episode duration ascertained at baseline over 30 days) and key cardiovascular outcomes. RESULTS: Among 39 710 patients (mean age 77.1±8.7 years, 60.7% male, and a mean CHA2DS2-VASc score 4.9±1.3), all-cause mortality at 1-year increased with baseline AF burden: 8.54% with AF burden 0%, 8.9% with AF burden 0% to 5%, and 10.9% with AF burden 5% to 98% (P<0.001) There was also a dose-response relationship between increasing AF burden and all-cause or cardiovascular hospitalization and ischemic stroke. Updating AF burden data every 30 days did not alter the AF burden-prognostic relationships determined from the use of baseline data alone. Results were also consistent when 3-year outcomes were considered and after accounting for the use of oral anticoagulants. CONCLUSIONS: In paroxysmal AF, there is a clinically relevant dose-response relationship between increasing AF burden and rates of adverse outcomes at 1- and 3-years, including increasing risks of cardiovascular hospitalization, ischemic stroke, and mortality.

Bimodal distribution of atrial fibrillation burden in 3 distinct cohorts: What is 'paroxysmal' atrial fibrillation?

BACKGROUND: Burden of atrial fibrillation (AF), as a continuous measure, is an emerging alternative classification often assumed to increase linearly with progression of disease. Yet there are no descriptions of AF burden distributions across populations. METHODS: We examined patterns of AF burden (% time in AF) across 3 different cohorts: outpatients with AF undergoing Holter monitoring in a national registry (ORBIT-AF II), routine outpatients undergoing Holter monitoring in a tertiary healthcare system (UHealth), and patients >= 65 years with cardiac implantable electronic devices (Merlin.netTM linked to Medicare). RESULTS: We included 2,058 ORBIT-AF II patients, 4,537 UHealth patients, and 39,710 from Merlin.net. Mean age ranged from 56 to 77 years, sex ranged from 40% to 61% male, and mean CHA2DS2-VASc scores ranged from 2.2 to 4.9. Across all cohorts, AF burden demonstrated skewed frequency towards the extremes, with the vast majority of patients having either very low or very high AF burden. This bimodal distribution was consistent across cohorts, across clinically-documented AF types (paroxysmal v persistent), patients with or without a known AF diagnosis, and among patients with different types of cardiac implantable electronic devices. CONCLUSIONS: Across 3 broad, diverse cohorts with continuous monitoring, distribution of AF burden was consistently skewed towards the extremes without an even, linear distribution or progression. As AF burden is increasingly recognized as a descriptor and potential risk-stratifier, these findings have important implications for future research and patient care.

Association between economic and arrhythmic burden of paroxysmal atrial fibrillation in patients with cardiac implanted electronic devices.

BACKGROUND: As the prevalence of atrial fibrillation (AF) increases, a greater understanding of the costs associated with AF care is required. While individuals with greater arrhythmic burden may interact with the health system more frequently, the relationship between AF burden and costs remains undefined. METHODS: In a longitudinal patient cohort with paroxysmal AF and newly implanted cardiovascular implantable electronic devices (CIED) (2010-2016), we linked CIED remote-monitoring data with Medicare claims to assess the association between the 30-day averaged device-detected daily percentage of time in AF ("AF burden") and healthcare costs. RESULTS: Among 39,345 patients, the mean age was 77.1 ± 8.7 years, 60.7% were male, and the mean CHA2DS2-VASc score was 4.9 ± 1.3. The mean total 1-year costs were $18,668 ± 29,173, driven by hospitalization costs where two-thirds of admissions were due to heart failure. Increasing AF burden was associated with increasing costs: $17,860 ± 28,525 for 0% daily AF burden; $18,840 ± 29,104 for 0-5% daily AF burden; and $20,968 ± 31,228 for 5-98% daily AF burden. There was a linear relationship between AF burden expressed as a continuous variable and 1-year costs (adjusted cost rate ratio 1.031 per 10% daily duration in AF, 95% confidence interval 1.023-1.038; P < .001). CONCLUSIONS: Among older patients with paroxysmal AF and CIEDs, increasing AF burden is associated with higher healthcare costs. As the observational study design is unable to determine causal relationships, prospective study is required to explore the intriguing hypothesis that targeted AF strategies, including comorbidity management, that reduce AF burden may also reduce the high annual costs associated with AF.

Flash CGM associated with event reduction in nonintensive diabetes therapy.

OBJECTIVES: We evaluated the effects of acquiring a flash continuous glucose monitoring (CGM) system in the population with type 2 diabetes (T2D) treated with basal or noninsulin therapy. STUDY DESIGN: This was a retrospective database analysis of the IBM MarketScan Commercial Claims and Medicare Supplemental databases that assessed rates of acute diabetes-related events (ADEs) and all-cause inpatient hospitalizations (ACHs) in a large population with T2D treated with basal insulin therapy or noninsulin medications. ADE and ACH rates 6 months prior to and 6 months post CGM acquisition were compared. METHODS: Inclusion criteria for analysis were diagnosis of T2D; age 18 years or older; treatment with long-acting, neutral protamine Hagedorn, or premixed insulin or noninsulin therapy; naïve to CGM; and acquisition of their flash CGM system between October 2017 and March 2019. Patients served as their own controls. Event rates were compared using weighted Cox regression with Andersen-Gill extension for repeat events. RESULTS: A cohort of 10,282 adults with T2D (mean [SD] age, 53.1 [9.6] years; 51.9% male) who met inclusion criteria were assessed. ADE rates decreased from 0.076 to 0.052 events per patient-year (HR, 0.68; 95% CI, 0.58-0.80; P < .001). ACH rates decreased from 0.177 to 0.151 events per patient-year (HR, 0.85; 95% CI, 0.77-0.94; P = .002). CONCLUSIONS: Acquisition of the flash CGM system was associated with significant reductions in outpatient and inpatient ADEs and ACHs. These findings provide compelling evidence that use of flash CGM in patients with T2D treated with basal insulin therapy or noninsulin therapy improves clinical outcomes and potentially reduces costs.

Real-world Adoption of Smartphone-based Remote Monitoring Using the Confirm Rx™ Insertable Cardiac Monitor.

While previous generations of insertable cardiac monitors (ICMs) required a bedside monitor for remote monitoring (RM), the Confirm Rx™ ICM (Abbott, Chicago, IL, USA) utilizes Bluetooth®, Wi-Fi/cellular technology, and a smart device to connect to the RM system. We aimed to characterize compliance, connectivity, and event transmission timing with the Confirm Rx™ ICM RM system. The study cohort included American patients who received the Confirm Rx™ ICM with SharpSense™ technology within three months of release (May-July 2019). Compliance with RM was quantified as the proportion of patients registering the patient app on their smart device and transmitting at least once. Connectivity was measured as the median number of days between consecutive transmissions per patient. Event transmission time was measured from episode detection to availability on the Merlin.net™ RM system (Abbott). Time from transmission until review by a clinician was examined. Values for device connectivity, episode transmission timing, and clinician view times were reported as median [first quartile, third quartile]. Of 5,666 patients who received a Confirm Rx™ ICM, 97% registered their patient app and 92% transmitted data at least once. Among those utilizing RM (aged 66 ± 15 years; 49% female), connectivity occurred every 1.5 [1.2, 2.4] days, or 4.7 times per week. Patient-reported symptoms were transmitted to Merlin.net™ within 2.9 [2.1, 3.8] minutes of event onset and viewed by the clinician within 0.9 [0.4, 3.1] days, while device-detected episodes without symptoms were transmitted within 18.5 [11.2, 36.5] hours and then viewed within 0.8 [0.3, 2.5] days. This real-world study demonstrated excellent patient compliance with the smartphone-based RM paradigm enabled by Confirm Rx™, suggesting the suitability of this technology for future cardiac implantable devices.

The cost of non-response to cardiac resynchronization therapy: characterizing heart failure events following cardiac resynchronization therapy.

AIMS: The aim of this study is to quantify healthcare resource utilization among non-responders to cardiac resynchronization therapy (CRT-NR) by heart failure (HF) events and influence of comorbidities. METHODS AND RESULTS: The ADVANCE CRT registry (2013-2015) prospectively identified responders/CRT-NRs 6 months post-implant using the clinical composite score. Heart failure event rates and associated cost, both overall and separated for inpatient hospitalizations, office visits, emergency room visits, and observational stays, were quantified. Costs of events were imputed from payments for similar real-world encounters in subjects with CRT-D/P devices in the MarketScan™ commercial and Medicare Supplemental insurance claims databases. Effects of patient demographics and comorbidities on event rates and cost were evaluated. Of 879 US patients (age 69 ± 11 years, 29% female, ischaemic disease 52%), 310 (35%) were CRT-NR. Among CRT-NRs vs. responders, more patients developed HF (41% vs. 11%, P < 0.001), HF event rate was higher (67.0 ± 21.7 vs. 11.4 ± 3.7/100 pt-year, P < 0.001), and HF readmission within 30 days was more common [hazard ratio 7.06, 95% confidence interval (2.1-43.7)]. Inpatient hospitalization was the most common and most expensive event type in CRT-NR. Comorbid HF was increased by diabetes, hypertension, and pulmonary disorders. Over 2 years, compared to CRT responders, each CRT-NR resulted in excess cost of $6388 ($3859-$10 483) to Medicare (P = 0.015) or $10 197 ($6161-$17 394) to private insurances (P = 0.014). CONCLUSION: Healthcare expenditures associated with contemporary CRT non-response management are among the highest for any HF patient group. This illustrates an unmet need for interventions to improve HF outcomes and reduce costs among some CRT recipients.

Early Increased Physical Activity, Cardiac Rehabilitation, and Survival After Implantable Cardioverter-Defibrillator Implantation.

BACKGROUND: Increased physical activity (PA) through cardiac rehabilitation (CR) improves outcomes in patients with heart failure and coronary disease, but CR referral remains infrequent. Implantable cardioverter-defibrillators (ICDs) can provide daily PA measurements to patients that may motivate them to increase PA, but it remains unclear if increased ICD measured PA is associated with improved outcomes with and without CR. METHODS: This is a retrospective observational study of 41 731 Medicare beneficiaries with ICD implantation between January 1, 2014 and December 31, 2016. We linked daily ICD PA measurements and Medicare claims data to determine if increased PA is associated with a reduction in the likelihood of death or heart failure hospitalization. To determine if CR participation altered the effect of PA on outcomes, we performed two additional analyses matching CR participants and nonparticipants using propensity scores. The first match included demographics, comorbidities, and baseline PA measurements. The second match also included the change in PA measured during CR or the same time frame after ICD implant among nonparticipants. RESULTS: The mean age was 75 (SD, 10) years, 30 182 beneficiaries (72.3%) were male, and 1324 (3%) participated in CR. Increased ICD detected PA was associated with improved survival. CR participants had a mean PA change of +9.7 (SD, 57.8) min/d, whereas nonparticipants had a mean change of -1.0 (SD, 59.7) min/d (P<0.001). After matching for demographics, comorbidities and baseline PA, CR participants had significantly lower 1- to 3-year mortality (hazard ratio, 0.76 [95% CI, 0.69-0.85], P=0.03). After additionally matching for the ICD measured change in PA during CR there were no differences in mortality with and without CR (hazard ratio, 1.00 [95% CI, 0.82-1.21], P=0.87). Every 10 minutes of increased daily PA was associated with a 1.1% reduction in all-cause mortality in both groups. CONCLUSIONS: Among Medicare beneficiaries with ICDs, small increases in PA were associated with significant reductions in all-cause mortality.

Use of Flash Continuous Glucose Monitoring Is Associated With A1C Reduction in People With Type 2 Diabetes Treated With Basal Insulin or Noninsulin Therapy.

BACKGROUND: Glycemic control is suboptimal in many individuals with type 2 diabetes. Although use of flash continuous glucose monitoring (CGM) has demonstrated A1C reductions in patients with type 2 diabetes treated with a multiple daily injection or insulin pump therapy regimen, the glycemic benefit of this technology in patients with type 2 diabetes using nonintensive treatment regimens has not been well studied. METHODS: This retrospective, observational study used the IBM Explorys database to assess changes in A1C after flash CGM prescription in a large population with suboptimally controlled type 2 diabetes treated with nonintensive therapy. Inclusion criteria were diagnosis of type 2 diabetes, age <65 years, treatment with basal insulin or noninsulin therapy, naive to any CGM, baseline A1C ≥8%, and a prescription for the FreeStyle Libre flash CGM system during the period between October 2017 and February 2020. Patients served as their own control subject. RESULTS: A total of 1,034 adults with type 2 diabetes (mean age 51.6 ± 9.2 years, 50.9% male, baseline A1C 10.1 ± 1.7%) were assessed. More patients received noninsulin treatments (n = 728) than basal insulin therapy (n = 306). We observed a significant reduction in A1C within the full cohort: from 10.1 ± 1.7 to 8.6 ± 1.8%; Δ -1.5 ± 2.2% (P <0.001). The largest reductions were seen in patients with a baseline A1C ≥12.0% (n = 181, A1C reduction -3.7%, P <0.001). Significant reductions were seen in both treatment groups (basal insulin -1.1%, noninsulin -1.6%, both P <0.001). CONCLUSION: Prescription of the flash CGM system was associated with significant reductions in A1C in patients with type 2 diabetes treated with basal insulin or noninsulin therapy. These findings provide evidence for expanding access to flash CGM within the broader population of people with type 2 diabetes.

Gain in real-world cardiac resynchronization therapy efficacy with SyncAV dynamic optimization: Heart failure hospitalizations and costs.

BACKGROUND: SyncAV, a device-based cardiac resynchronization therapy (CRT) algorithm, promotes electrical optimization by dynamically adjusting atrioventricular intervals. OBJECTIVE: The purpose of this study was to evaluate the impact of SyncAV on heart failure hospitalizations (HFHs) and related costs in a real-world CRT cohort. METHODS: Patients with SyncAV-capable CRT devices followed by remote monitoring and enrolled in Medicare fee-for-service for at least 1 year preimplant and up to 2 years postimplant were studied. Patients with SyncAV OFF were 4:1 matched to those with SyncAV ON on preimplant HFH rate, demographics, comorbidities, disease etiology, and left bundle branch block. HFHs were determined from the primary diagnosis of inpatient hospitalizations, and the cost for each event was the sum of Medicare, supplemental insurance, and patient payment. RESULTS: After 4:1 propensity score matching, 3630 patients were studied (mean age 75 ± 8 years; 1386 [38%] female), including 726 (25%) patients with SyncAV ON. The pre-CRT HFH rate was 0.338 HFH events per patient-year. Overall, CRT diminished the HFH rate to 0.204 events per patient-year (P < .001). SyncAV elicited a larger reduction in HFH rate (SyncAV ON: hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.41-0.66; P < .001 and SyncAV OFF: HR 0.68; 95% CI 0.59-0.77; P < .001). After 2 years, the HFH rate was lower in the SyncAV ON group than in the SyncAV OFF group (0.143 HFHs per patient-year vs 0.193 HFHs per patient-year; HR 0.70; 95% CI 0.55-0.89; P = .003) and fewer HFHs were followed by 30-day HFH readmissions (4.41% vs 7.68%; P = .003) and 30-day all-cause hospital readmissions (7.04% vs 10.01%; P = .010). The total 2-year HFH-associated costs per patient were lower with SyncAV ON (difference $1135; 90% CI $93-$2109; P = .038). CONCLUSION: This large, real-world, propensity score-matched study demonstrates that SyncAV CRT is associated with significantly reduced HFHs and associated costs, incremental to standard CRT.

Flash CGM Is Associated With Reduced Diabetes Events and Hospitalizations in Insulin-Treated Type 2 Diabetes.

PURPOSE: Suboptimal glycemic control among individuals with diabetes is a leading cause of hospitalizations and emergency department utilization. Use of flash continuous glucose monitoring (flash CGM) improves glycemic control in type 1 and type 2 diabetes, which may result in lower risk for acute and chronic complications that require emergency services and/or hospitalizations. METHODS: In this retrospective, real-world study, we analyzed IBM MarketScan Commercial Claims and Medicare Supplemental databases to assess the impact of flash CGM on diabetes-related events and hospitalizations in a cohort of 2463 individuals with type 2 diabetes who were on short- or rapid-acting insulin therapy. Outcomes were changes in acute diabetes-related events (ADE) and all-cause inpatient hospitalizations (ACH), occurring during the first 6 months after acquiring the flash CGM system compared with event rates during the 6 months prior to system acquisition. ICD-10 codes were used to identify ADE for hypoglycemia, hypoglycemic coma, hyperglycemia, diabetic ketoacidosis, and hyperosmolarity. RESULTS: ADE rates decreased from 0.180 to 0.072 events/patient-year (hazard ratio [HR]: 0.39 [0.30, 0.51]; P < 0.001) and ACH rates decreased from 0.420 to 0.283 events/patient-year (HR: 0.68 [0.59 0.78]; P < 0.001). ADE reduction occurred regardless of age or gender. CONCLUSIONS: Acquisition of the flash CGM system was associated with reductions in ADE and ACH. These findings provide support for the use of flash CGM in type 2 diabetes patients treated with short- or rapid-acting insulin therapy to improve clinical outcomes and potentially reduce costs.

Atrial fibrillation burden and heart failure: Data from 39,710 individuals with cardiac implanted electronic devices.

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) often accompany one another, and each is independently associated with poor outcomes. However, the association between AF burden and outcomes is poorly understood. OBJECTIVE: The purpose of this study was to describe the association between device-based AF burden and HF clinical outcomes. METHODS: We used a nationwide, remote monitoring database of cardiac implantable electronic devices (CIEDs) linked to Medicare claims. We included patients with nonpermanent AF, undergoing new CIED implant, stratified by baseline HF. The outcomes were new-onset HF, HF hospitalization, and all-cause mortality at 1 and 3 years. RESULTS: We identified 39,710 patients who met inclusion criteria (25,054 with HF; 14,656 without HF). Patients with HF were younger (mean age 76.3 vs 78.5 years; P <.001), more often male (65% vs 54%; P <.001), and had higher mean CHA2DS2-VASc scores (5.4 vs 4.1; P <.001). Among those without HF, increasing device-based AF burden was significantly associated with increased risk of new-onset HF (adjusted hazard ratio [HR] 1.09 per 10% AF burden; 95% confidence interval [CI] 1.06-1.12; P <.001) and all-cause mortality (adjusted HR 1.05 per 10% AF burden; 95% CI 1.01-1.10; P = .012). Among patients with HF, increasing AF burden was significantly associated with increased risk of HF hospitalization (adjusted HR 1.05 per 10% AF burden; 95% CI 1.04-1.06; P <.001) and all-cause mortality (adjusted HR 1.06 per 10% AF burden; 95% CI 1.05-1.08; P <.001). CONCLUSION: Among older patients with AF receiving a CIED, increasing AF burden is significantly associated with increasing risk of adverse HF outcomes and all-cause mortality.

Clinical and economic impact of multipoint left ventricular pacing: A comparative analysis from the Italian registry on multipoint pacing in cardiac resynchronization therapy (IRON-MPP).

INTRODUCTION: Early evidence suggests that multipoint left ventricular pacing (MPP) may improve response to cardiac resynchronization therapy (CRT). It is unknown whether this benefit is sustained and cost-effective. We used real-world data to evaluate long-term impact of MPP-ON clinical status, heart failure hospitalizations (HFH) and costs. METHODS: The Italian registry on multipoint left ventricular pacing is a prospective, multicenter registry of patients implanted with MPP-enabled CRT devices. For this analysis, clinical and echocardiographic data were collected through 24 months and compared between patients with (MPP-ON) or without (MPP-OFF) early MPP activation at implant. The total cost of each HFH was estimated with national Italian reimbursement rates. RESULTS: The study included 190 MPP-OFF and 128 MPP-ON patients with similar baseline characteristics. At 1 and 2 years, the MPP-ON group had lower rates of HFH vs MPP-OFF (1-year hazard ratio [HR]: 0.14, P = .0014; 2-year HR: 0.38, P = .009). The finding persisted in a subgroup of patients with consistent MPP activation through follow-up (1-year HR: 0.19; P = .0061; 2-year HR: 0.39, P = .022). Total HFH per-patient costs were lower in the MPP-ON vs the MPP-OFF group at 1 year (€101 ± 50 vs €698 ± 195, P < .001) and 2 years (€366 ± 149 vs €801 ± 203, P = .038). More MPP-ON patients had ≥5% improvement in ejection fraction (76.8% vs 65.4%, P = .025) and clinical composite score (66.7% vs 47.5%, P = .01). CONCLUSIONS: In this multicenter clinical study, early MPP activation was associated with a significant reduction in cumulative HFH and related costs after 1 and 2 years of follow-up.

Effect of High Influenza Activity on Risk of Ventricular Arrhythmias Requiring Therapy in Patients With Implantable Cardiac Defibrillators and Cardiac Resynchronization Therapy Defibrillators.

Influenza is associated with an increased risk of cardiovascular events. Influenza's association with ventricular arrhythmias (VAs) has not been adequately studied. We investigated the relation of seasonal influenza activity with the incidence of VAs requiring therapy in patients with an implantable cardiac defibrillator or cardiac resynchronization therapy defibrillator. We retrospectively studied 163,831 patients with an implantable cardiac defibrillator or cardiac resynchronization therapy defibrillator who were enrolled in the Abbott Medical Merlin.net remote-monitoring network between January 2009 and December 2015. We used cross-correlation to assess the temporal relationship between influenza activity and the incidence of VAs requiring shock or antitachycardia pacing (ATP). We used a generalized linear model to test the possible effect of seasonal influenza activity on the occurrence of VAs requiring shock or ATP treatment, after adjustment for within-patient effects, age, gender, device type, and calendar year. We found a significant correlation between influenza activity and the incidence of VAs requiring shock or ATP treatment. The multivariate generalized linear model showed that during high influenza activity, patients were more likely to have a VA treated with shock (odds ratio = 1.06, p < 0.001) or ATP (odds ratio = 1.06, p < 0.0001). The impact of high influenza activity was most prominent during the years 2014 and 2015. We conclude that high influenza activity is associated with increased risk of VAs requiring therapy.

Atrial fibrillation burden, progression, and the risk of death: a case-crossover analysis in patients with cardiac implantable electronic devices.

AIMS: Atrial fibrillation (AF) is associated with increased mortality, but the temporal relationship between AF burden (AFB) and death among patients with cardiac implanted electronic devices is unknown. We sought to characterize the timing and progression of AFB before death. METHODS AND RESULTS: Using Merlin.netTM remote monitoring (RM) data, we analysed weekly AFB in patients age ≥55 years implanted with dual-chamber pacemaker, implantable cardioverter-defibrillator, or cardiac resynchronization therapy devices whose death was verified in the Social Security Death Index and who had continuous RM from 1 year to 4 weeks preceding death. Atrial fibrillation burden was defined as amount of time per week atrial rate exceeded a set threshold of 180 b.p.m. Case-crossover analysis was used to compare the AFB at every week to 6 control weeks at the start of the year before death. There were 3131 patients meeting analysis criteria (age at death 76 ± 8 years, 70% men). Weekly increase in AFB >6 h was associated with increased odds of death, which was greatest at 4 weeks before death [odds ratio (OR) 2.30, 95% confidence interval (CI) 2.09-2.53; P < 0.001]. Atrial fibrillation progression week-to-week >24 h was associated with the greatest odds of death (OR 12.95, 95% 8.72-19.22; P < 0.001). A combination of AFB >6 h per week and activity <0.5 h per day was associated with an increased odds of death. CONCLUSION: In this large patient cohort, AFB progression accelerated in the weeks leading to death. Continuous monitoring of AFB may help identify device patients who may be at risk for adverse outcomes, including death.

Comparative study of acute and mid-term complications with leadless and transvenous cardiac pacemakers.

BACKGROUND: Leadless cardiac pacemakers (LCPs) aim to mitigate lead- and pocket-related complications seen with transvenous pacemakers (TVPs). OBJECTIVE: The purpose of this study was to compare complications between the LCP cohort from the LEADLESS Pacemaker IDE Study (Leadless II) trial and a propensity score-matched real-world TVP cohort. METHODS: The multicenter LEADLESS II trial evaluated the safety and efficacy of the Nanostim LCP (Abbott, Abbott Park, IL) using structured follow-up, with serious adverse device effects independently adjudicated. TVP data were obtained from Truven Health MarketScan claims databases for patients implanted with single-chamber TVPs between April 1, 2010 and March 31, 2014 and more than 1 year of preimplant enrollment data. Comorbidities and complications were identified via International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Short-term (≤1 months) and mid-term (>1-18 months) complications were compared between the LCP cohort and a propensity score-matched subset of the TVP cohort. RESULTS: Among 718 patients with LCPs (mean age 75.6 ± 11.9 years; 62% men) and 1436 patients with TVPs (mean age 76.1 ± 12.3 years; 63% men), patients with LCPs experienced fewer complications (hazard ratio 0.44; 95% confidence interval 0.32-0.60; P < .001), including short-term (5.8% vs 9.4%; P = .01) and mid-term (0.56% vs 4.9%; P < .001) events. In the short-term time frame, patients with LCPs had more pericardial effusions (1.53% vs 0.35%; P = .005); similar rates of vascular events (1.11% vs 0.42%; P = .085), dislodgments (0.97% vs 1.39%; P = .54), and generator complications (0.70% vs 0.28%; P = .17); and no thoracic trauma compared to patients with TVPs (rate of thoracic trauma 3.27%). In short- and mid-term time frames, TVP events absent from the LCP group included lead-related, pocket-related, and infectious complications. CONCLUSION: Patients with LCPs experienced fewer overall short- and mid-term complications, including infectious and lead- and pocket-related events, but more pericardial effusions, which were uncommon but serious.

Increased Hospitalizations and Overall Healthcare Utilization in Patients Receiving Implantable Cardioverter-Defibrillator Shocks Compared With Antitachycardia Pacing.

OBJECTIVES: The purpose of this study was to evaluate the effect of these therapies on healthcare utilization in a large patient cohort. BACKGROUND: Antitachycardia pacing (ATP) terminates ventricular tachycardia and avoids delivery of high-voltage shocks. Few data exist on the impact of shocks on healthcare resource utilization compared with ATP. METHODS: PROVIDE (Programming Implantable Cardioverter Defibrillators in Patients With Primary Prevention Indication) was a prospective study of patients who received an implantable cardioverter-defibrillator (ICD) for primary prevention at 97 U.S. centers (2008 to 2010). We categorized the PROVIDE patients by the type of therapy delivered: no therapy, ATP only, or at least 1 shock. All ICD therapies, hospitalizations, and deaths were adjudicated. Cumulative cardiac hospitalizations, risk of all-cause death or cardiac hospitalization, and annual costs were compared between groups. RESULTS: Of the 1,670 patients in PROVIDE, followed up for 18.1 ± 7.6 months, 1,316 received no therapy, 152 had ATP only, and 202 received at least 1 shock. Patients receiving no therapy and those receiving only ATP had a lower cumulative hospitalization rate and were at lower risk for death or hospitalization (hazard ratio: 0.33 [p < 0.001] and 0.33 [p < 0.002], respectively). The cost of hospitalization was $2,874 per patient-year (95% confidence interval: $877 to $5,140; p = 0.002) higher for those receiving at least 1 shock than for those who received ATP only. There was no difference in outcomes or cost between patients receiving only ATP and those without therapy. CONCLUSIONS: Among patients implanted with an ICD for primary prevention, those who received only ATP therapy had reduced hospitalizations, mortality, and cost compared with those who received at least 1 high-voltage shock and had equivalent outcomes to patients who did not require any therapy. (Programming Implantable Cardioverter Defibrillators in Patients With Primary Prevention Indication [PROVIDE]; NCT00743522).